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M04.02.02 The cell cycle
The cell cycle is the process by which a cell replicates its genetic material and divides into two identical daughter cells. This is a tightly regulated process essential for growth, development, and tissue repair. This article covers the phases of the cell cycle, the regulation mechanisms that ensure correct progression, and the clinical relevance of cell cycle dysregulation.
Phases of the Cell Cycle
The cell cycle is divided into four main stages:
- G1 (Gap 1) phase: The cell grows in size and duplicates its organelles.
- S (Synthesis) phase: DNA replication occurs, and the cell duplicates its chromosomes.
- G2 (Gap 2) phase: The cell grows further and prepares for division by synthesizing organelles and proteins.
- M (Mitosis) phase: The cell undergoes mitosis (nuclear division) and cytokinesis (cell division) to produce two identical daughter cells.
Additionally, some cells enter a quiescent state known as the G0 phase, where they are not actively dividing.
Table: Key Phases of the Cell Cycle
| Phase | Key Processes |
|---|---|
| G1 phase | Cell growth, duplication of organelles |
| S phase | DNA replication, chromosome duplication |
| G2 phase | Cell growth, preparation for mitosis |
| M phase | Mitosis (nuclear division), cytokinesis (cell division) |
| G0 phase | Resting state, no cell division |
Interphase
Interphase includes the G1, S, and G2 phases, during which the cell is preparing for mitosis. These phases are collectively referred to as interphase because the cell spends most of its time here growing and replicating DNA before undergoing mitosis.
G0 Phase: Quiescent State
- Some cells exit the G1 phase and enter G0, where they remain inactive in terms of cell division.
- Terminal differentiation occurs in cells that permanently remain in G0, such as neurons and muscle cells.
- Some cells may re-enter the cycle upon receiving the appropriate signals.
Regulation of the Cell Cycle
The progression through the cell cycle is regulated by multiple checkpoints to ensure proper DNA replication and division. These checkpoints prevent cells with damaged DNA from continuing through the cycle, reducing the risk of mutations and cancer development.
Key Regulatory Mechanisms
- Checkpoints: Critical control points, especially at G1, S, and G2 phases, ensure that cells only proceed if they have intact DNA.
- G1 checkpoint (R point): Major checkpoint that decides whether a cell commits to the cycle.
- G2/M checkpoint: Ensures DNA is fully replicated and undamaged before mitosis.
- Spindle checkpoint: Ensures proper chromosome alignment during mitosis.
- p53 Protein: A tumor suppressor gene that plays a crucial role in detecting DNA damage. When damage is detected, p53 halts the cell cycle to allow for repair. If repair is not possible, p53 initiates apoptosis (programmed cell death).
- Cyclins and CDKs: Cyclins are proteins that regulate the activity of cyclin-dependent kinases (CDKs), which control cell cycle progression by phosphorylating key substrates.
Table: Major Checkpoints and Regulators
| Checkpoint | Detects DNA damage halts cycle, initiates repair or apoptosis |
|---|---|
| G1 checkpoint | Ensures cell size and DNA integrity before S phase |
| G2/M checkpoint | Confirms DNA replication is complete before mitosis |
| Spindle checkpoint | Ensures proper chromosome alignment in mitosis |
| p53 | Detects DNA damage, halts cycle, initiates repair or apoptosis |
| Cyclins & CDKs | Control progression through various stages of the cycle |
Retinoblastoma Protein (Rb)
- Rb protein: Inhibits progression from the G1 to S phase. When phosphorylated by CDKs, Rb becomes inactive, allowing the cell to progress through the cycle. Mutations in Rb or loss of its function can lead to uncontrolled cell growth.
Clinical Relevance: Neoplasia
Neoplasia is a condition characterized by uncontrolled cell division, often caused by mutations in cell cycle regulators such as p53 or Rb.
- Mutated p53: Inability to stop the cycle when DNA is damaged, leading to unchecked cell division and increased risk of tumor formation.
- Oncogenes and Tumor Suppressors: Mutations in genes that control cell proliferation (oncogenes) or those that suppress tumors (like p53 and Rb) can result in cancer.
Points to Remember:
- The cell cycle consists of G1, S, G2, and M phases.
- G1, S, and G2 phases together form interphase.
- G0 is a quiescent state for non-dividing cells.
- Checkpoints regulate the cycle, preventing damaged cells from dividing.
- p53 and Rb are crucial in preventing uncontrolled cell proliferation.
- Dysregulation of the cell cycle can lead to cancer.
Bibliography:
- Weller, George. The Cell Cycle [Image]. Wikimedia Commons. Available at: https://commons.wikimedia.org/wiki/File:The_Cell_Cycle.svg. License: CC BY-SA 3.0.
- CNX OpenStax. Important Checkpoints and Regulators of the Cell Cycle [Image]. Wikimedia Commons. Available at: https://commons.wikimedia.org/wiki/File:Figure_10_03_01.jpg. License: CC BY 4.0.
